Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus

Hyungju Jeon, Hojin Lee, Dae Hyuk Kwon, Jiwon Kim, Keiko Tanaka-Yamamoto, Jang Soo Yook, Linqing Feng, Hye Ran Park, Yong Hoon Lim, Zang Hee Cho, Sun Ha Paek, Jinhyun Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN. Our circuit- and cellular-level connectivities reveal a topographically graded organization with three types of indirect and hyperdirect pathways (external globus pallidus only, STN only, and collateral). We confirm consistent pathways into the human STN by 7 T MRI-based tractography. We identify two functional types of topographically distinct glutamatergic STN neurons (parvalbumin [PV+/−]) with synaptic connectivity from indirect and hyperdirect pathways. Glutamatergic PV+ STN neurons contribute to burst firing. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

Original languageEnglish
Article number110439
JournalCell Reports
Volume38
Issue number9
DOIs
StatePublished - 1 Mar 2022

Keywords

  • cell type
  • connectivity
  • firing pattern
  • indirect and hyperdirect pathways
  • subthalamic nucleus

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